Introduction

Diagnosing and assessing Inflammatory Bowel Disease (IBD) requires invasive procedures such as endoscopy and intestinal biopsies. However, reliable and accurate non-invasive tools for assessing and monitoring inflammation in IBD patients are in an exciting phase of early development. Raman spectroscopy (RS), which provides molecular vibrational spectra, can characterise human biofluids and intestinal samples, offering the potential for non-invasive molecular assessment, characterisation and monitoring in IBD.

Aims & Methods

This study aims to explore the potential of RS applied to saliva, blood and intestinal biopsies from IBD patients for molecular characterisation and development of new biomarkers enabling a reliable and accurate non-invasive diagnosis of IBD, phenotyping between Crohn’s disease (CD) and Ulcerative Colitis (UC) and predicting mucosal healing (MH). IBD patients undergoing advanced endoscopy, i.e. ultra-high magnification endocytoscopy or probe-based confocal laser endomicroscopy, for disease assessment or surveillance and healthy controls were prospectively enrolled from two university hospitals in Cork, Ireland. Peripheral blood, saliva, and biopsies from the most representative bowel areas were collected. All matching samples were processed through a novel waveguide-enhanced RS technique, enabling sensitive detection of metabolites and other biochemical components. Additionally, MH from matching biopsies was assessed as RHI≤3 without lamina propria or epithelial neutrophils, NHI ≤1 and PHRI=0. RS data processing was performed using Matlab®. Spectral markers matched for saliva, blood and biopsies and differentiating IBD vs controls, CD vs UC and MH vs active inflammation were identified. A machine learning model based on linear discrimination analysis was used to assess the classification accuracy.

Results

A cohort of 16 IBD patients (median age 39, 11:5 M: F), comprising 9 UC and 7 CD, and 4 healthy controls (median age 43.5, 3:1 M: F) was enrolled, with matching saliva, blood, and biopsies. MH was found in 4 IBD patients. When comparing IBD patients with controls, differences in 3 wavenumbers were observed in all samples, corresponding to decreased tyrosine and lipids signals and increased carotenoids signal in IBD. Similarly, differences in spectral markers were found in CD vs UC, with increased lipids signal in CD and increased signals for carotenoids, nucleic acid, and amide proteins in UC. Interestingly, 5 matching differences in saliva, plasma and biopsies spectra were found in patients with MH compared to those with active inflammation, including an increase in nucleic acids and amide proteins and a decrease in phosphate, lipids, and carotenoids. The machine learning model showed promising accuracy (above 82%) of RS-aided biofluids analysis in diagnosing IBD and predicting phenotype and MH.

Conclusion

The combination of spectral markers from saliva and plasma, confirmed at tissue level, showed promise in accurately diagnosing IBD and distinguishing CD from UC. Notably, RS non-invasive biomarkers could predict MH with promising accuracy, identifying metabolites involved in IBD-associated inflammation, particularly lipids, carotenoids, and nucleic acids. Therefore, RS holds potential as a monitoring and predictive tool for inflammation and healing in IBD, with intriguing translational implications. Further studies are required to validate these preliminary findings and shed light on molecular mechanisms.

Introduction

Nowadays there is no screening test approved on large scale for gastric cancer even if this neoplasia represents one of the leading causes of cancer-related deaths globally^1-2. In Italy still remains one of the most frequent tumors, with incidence rates differing across geographical areas³.

Aims & Methods

This project aims to create an easily administrable tool to detect anamnestic gastric cancer risk factors together with alarm symptoms in an age-defined target population to identify patients in need of an esophagogastroduodenoscopy (EGD).
This paper describes the first study phase: the administration of the questionnaire to a first sample of 5000 people aged from 40 to 80 years and the preliminary results. GASTROFORM is an online questionnaire (https://it.research.net/r/GASTROFORM) collecting data about demographic and anthropometric features, physiological anamnesis, familial history, non-specific upper gastrointestinal symptomatology, alarm symptoms and recent EGD performance.

Results

4426 valid questionnaires were submitted through the online form in November 2022, 612 of them (13,82%) reported at least one alarm symptom identifying patients in need to undergo an EGD as soon as possible. From an epidemiological point of view we expect to increase the rate of diagnosis in Barret esophagus (from 1,8% to 5-8%), atrophic gastritis (from 9% to 20-30%) and early gastric cancer (from 0,019% to 1-2 %).

Conclusion

The GASTROFORM questionnaire could provide useful informations to identify a population most likely to have significant endoscopic findings in early diagnosis during a screening EGD.

References

1. Ilic M, Ilic I. Epidemiology of stomach cancer. World J Gastroenterol. 2022;28(12):1187-1203. doi:10.3748/wjg.v28.i12.1187
2. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26-38. doi:10.5114/pg.2018.80001
3. Donida BM, Tomasello G, Ghidini M, et al. Epidemiological, clinical and pathological characteristics of gastric neoplasms in the province of Cremona: the experience of the first population-based specialized gastric cancer registry in Italy. BMC Cancer. 2019;19(1):212. Published 2019 Mar 8. doi:10.1186/s12885-019-5366-1

Introduction

Colorectal endoscopic submucosal dissection (ESD) is spreading worldwide, with increasing demand for training. Standardized skills assessment has yet to be defined to guarantee the quality and safety of the results obtained by trainees during their learning curve. ESGE recommends that the first ESD procedures should be supervised by an ESD-proficient endoscopist. The impact of a trainee's active participation on these initial supervised ESD results should be addressed.

Aims & Methods

Between 01/2017 and 01/2024, all consecutive colorectal ESD procedures were prospectively registered by 3 participating ESD training centers, and data were analyzed retrospectively. Trainee participation was tracked. A trainee was defined as having performed less than 50 ESD’s on humans, alone or under supervision. We compared the main procedural outcomes with respect to the presence or absence of a trainee involved in the colorectal ESD procedure. Multivariate analysis and propensity score matching (PSM) were performed.

Results

2462 consecutive colorectal ESD were included, of which 543 procedures (22%) involved the active participation of a trainee (15 trainers/15 trainees). Rectal lesions were more often treated with participation of a trainee (56% vs 31%, p<0.001 with-trainee vs trainer-alone respectively). There was no significant difference in en-bloc, R0 and curative resection rates whether a trainee participated or not (95.8%, 85.9% and 84.9% vs 95.1%, 88.2% and 84.7%, with-trainee vs trainer-alone respectively). Participation of a trainee resulted in a significant decrease in dissection speed (29.4 mm²/min vs 43.9 mm²/min, p<0.001 with-trainee vs trainer-alone respectively). Rates of perforation, delayed bleeding and surgery for complications were 8.6%, 5.9% and 0.9% vs 9%, 4.5% and 0.7% for with-trainee vs trainer-alone respectively, without significant differences. After PSM, the presence of a trainee significantly decreased the dissection speed (29.4 mm²/min vs 42.7 mm²/min, p<0.001 with-trainee vs trainer-alone respectively), increased the perforation rate (8.7% vs 5%, p=0.023 with-trainee vs trainer-alone respectively), but did not influence the curative resection rate (84.9% vs 88.8%, p=0.078 with-trainee vs trainer-alone respectively).

Conclusion

Active participation of a trainee during colorectal ESD did not affect the curative resection rate. However slower dissection speed and higher perforation rates, without increasing the need for surgery, were observed.

Disclosure

Nothing to disclose

Clinical Case Summary

Introduction: Inflammatory bowel disease (IBD) is linked to cutaneous manifestations in 10% of cases. Neutrophilic dermatoses represent a diagnostic and management challenge, as it requires a dual-targeted treatment approach.
Clinical Case: We present a 67-year-old man with A3L1B1 Crohn’s disease (CD) followed in our IBD consultation. His medical history included previous tobacco abuse, hypertension, type 2 diabetes and ischemic cardiopathy with heart failure. He was medicated for his comorbidities and had been treated with budesonide.
Due to evidence of disease progression, increased fecal calprotectin (FC) at 751ug/g and a history of invasive pulmonary aspergillosis, vedolizumab was initiated.
The patient presented with recurrent erythematous, tender, nodular lesions on the abdomen, limbs and face. Dermatological consultation and cutaneous biopsies led to an initial misdiagnosis of infectious panniculitis, as methicillin sensitive Staphylococcus aureus (MSSA) was isolated and the lesions regressed with antibiotics.
Two months later, cutaneous lesions reappeared and histopathology confirmed IBD-associated erythema nodosum-like neutrophilic dermatosis with MSSA isolation. A 10-week doxycycline course induced their regression. However, recurrence transpired 5 months later, associated with an increased FC (816ug/g).
A swap for ustekinumab (UST) resulted only in transient clinical and biochemical improvement (FC 324ug/g). Despite dose escalation to every 4 weeks, nodular/papular lesions with central postulation recently reappeared, prompting initiation of daptomycin with a potential swap to another drug class.
Conclusions: IBD can be associated with neutrophilic dermatoses and its diagnosis can be challenging. This case reports an CD-associated erythema nodosum-like neutrophilic dermatosis, underscoring its complex approach and management.
Note: We are submitting this case with iconography as it underscores a rare IBD manifestation.

References

Photographs of cutaneous lesions (3-4)

Clinical Case Summary

Introduction: Ustekinumab (UST), a human interleukin-12/23 monoclonal antibody, is approved for the treatment of moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). Some patients may lose response to standard maintenance therapy. Optimization strategies, such as dose escalation and intravenous (IV) re-induction, have been explored in CD, but scarcely studied in UC.
Clinical Case: A 61-year-old woman, with grade III obesity, hypertension, and peripheral venous insufficiency, diagnosed with UC and associated peripheral arthropathy, was initially treated with high-dose corticosteroids (CTS) for a severe exacerbation. She developed CTS dependence and suffered an osteoporotic fracture.
A combined therapy with methotrexate and an accelerated infliximab (IFX) induction regimen was initiated, but a severe exacerbation occurred after the second induction dose. Despite an early third dose, clinical, biochemical and endoscopic (Mayo score 3) activity persisted.
The patient was swapped to UST with maintenance therapy every 4 weeks. After IV infusion, free-CTS clinical and biochemical (fecal calprotectin (FC) <10 ug/g) remission were achieved, but, over time, there was a loss of response, with a FC 4817 ug/g.
Given the initial positive response to IV UST infusion and insights from CD studies, a 520mg IV UST re-induction followed by 4-week maintenance dose was administered. Eight months later, the patient remains in free-CTS clinical remission, with improved arthralgia, biochemical remission (FC 80 ug/g) and endoscopic response.
Conclusions: This case highlights the potential efficacy of IV UST re-induction in recapturing remission in refractory UC. While recognized in CD, UST re-induction may prove beneficial for UC patients with loss of response to standard UST therapy, serving as an alternative before swapping. Further exploration through randomized, multicenter studies is crucial to assess the efficacy and safety of this strategy in UC patients.